The University of the Witwatersrand's Wits HIV Research Group (WHRG) CTU is a well-established, multidisciplinary group of researchers active in HIV and TB prevention and treatment research. The group has a12 year track-record of NIAID funded Network research resulting in over 300 publications. The application is led by two experienced investigators, Dr. lan Sanne (MD), and Dr. Helen Rees (MD), who have complementary skills in HIV treatment and prevention. The leadership of the WHRG CTU has made significant scientific contributions to the research agenda of the NIAID-funded networks, and major contributions to HIV prevention and treatment public health policy and program implementation in South Africa and internationally. In this continuation application, WHRG presents a strong CTU that builds on the effective management, quality assurance and research infrastructure already in place, and expands the scope of the research at three clinical research sites (CRS) in Johannesburg: Wits Helen Joseph Hospital CRS (Wits HJH CRS), proposes to work with the Network on Therapeutics for HIV and HIV-associated Infections in Adults and the Network for Integrated Prevention Strategies; Wits Reproductive Health and HIV Institute CRS (WRHI CRS), proposes to work with the Network on Microbicides to Prevent HIV Infection, the Network on Integrated Strategies to Prevent HIV Infection, and the Network on HIV/AIDS and HIV-associated Infections in Pediatric and Maternal Populations. Sizwe Hospital CRS, an in-patient facility for MDRTB proposed to work with the Network on Therapeutics for HIV/AIDS and HIV associated infections in Adults to study therapeutics for MDRTB. Laboratory support provided by CLS and BARC, both active laboratories in the NIAID-funded Networks. This application describes Grants Management, Pharmacy, Data Management, Site Management, Quality Assurance and scientific expertise. The WHRG is an outstanding performer within the DAIDS CTU establishment. Wits HJH CRS is the highest performing site of the ACTG Network. WRHI has a strong track record in the NIAID Networks and has conducted numerous HIV prevention and treatment studies in adults and children. The proposed Sizwe CRS has completed FDA IND studies in novel drugs for MDR-TB. The WHRG has significant access to diverse HIV infected and uninfected pediatric and adult populations, making it ideally suited to respond to the existing and emerging priorities of the new networks. This application has significant institutional support from both Wits University and the Department of Health. RELEVANCE: Africa is at the epicenter of the HIV and Tuberculosis (TB) epidemics. In a country of 51.7 million people, adult HIV prevalence is 18%, with nearly 6 million people living with HIV, the largest number in any country worldwide. The TB epidemic also continues unabated, with an estimated 948 new cases of TB annually per 100,000 population. At the epicentre of the HIV epidemic, prevention and treatment research will lead to a change in the impact of HIV and TB on mortality and morbidity in South Africa.